The purpose of the protocol is to extensively test individuals for the disease tuberous sclerosis (TSC) who are members of families in which multiple members are affected with TSC. The individuals are enrolled through the CRC in a linkage study searching for the genes which cause TSC. Since the inception of the CRC study almost six years ago, much progress has been made on TSC. In 1992, linkage to chromosome 16p was reported by the United States TSC Collaborative Group, of which the PI is a participant. This information led to the cloning of the TSC2 gene in late 1993-early 1994. The PI is now detecting mutations in the TSC2 gene in affected individuals. The PI has initiated studies of tuberin, the TSC2 protein. Progress has also been made in the search for the TSC1 gene on chromosome 9q. The region is now smaller and candidate genes are being tested. The CRC portion of the study was completed in 1995. The PI is now focusing exclusively on the benchwork aspect of the disease.